Diuretics Flashcards
What is the primary function of diuretics? What do they treat (generally)?
Increase volume of urine
Treats edema
From what drug were the first diuretics all derived?
Sulfonilamide
What kinds of conditions can lead NaCl intake to exceed output?
CHF or Renal Failure
Leads to edema
About what % of NaCl is reabsorbed in the PCT?
65%
About what % of NaCl is reabsorbed in the thin descending limb?
0%
About what % of NaCl is reabsorbed in the thick ascending limb?
35%
About what % of NaCl is reabsorbed in the DCT?
10%
About what % of NaCl is reabsorbed in the collecting duct?
2-5%
How do most diuretics get into the luminal fluid? What is the exception?
Most reach the luminal fluid by organic acid and base secretion in the PCT. They are not filtered at the glomerulus because they are protein bound.
Mannitol is the exception and it is filtered at the glomerulus.
What transporters are present on the basal side of the PCT epithelium?
Na+/K+ ATPase
Na+/HCO3- cotransporter
Acetazolamide
MOA
Reversible inhibition of carbonic anhydrase
Inhibits reabsorption of HCO3- in the PCT
Acetazolamide
Adverse Effects
Metabolic acidosis (prevents HCO3- reabsorption into blood)
Hypokalemia
Calcium phosphate stones (decrease pH of the luminal fluid)
Acetazolamide
Contraindication
Cirrhosis
Increased urine pH leads to less NH3 excretion, therefore giving higher NH3 serum levels
List the four carbonic anhydrase inhibitors
Acetazolamide
Dichlorphenamide
Methazolamide
Dorzolamide
Acetazolamide
Clinical Uses
Diuretic (pretty weak)
Glaucoma (reduces intraocular pressure)
Urinary alkalinization
Acute mountain sickness (prophylaxis – decrease hemoglobin’s affinity for O2 so more O2 is deposited at tissues)
Mannitol is what kind of diuretic?
Where does mannitol have its major effects?
Osmotic Diuretic
Major effects in the PCT, descending limb of loop of Henle, collecting ducts (if ADH present)
How does mannitol reach the luminal fluid?
Gets filtered at the glomerulus.
Mannitol
Administration
IV only
Mannitol
Adverse Effects
Increased plasma osmolality
Moves water out of the cells into the ECF, which can worsen heart failure
Acute pulmonary edema
Dehydration
Mannitol
Clinical Indications
Maintain or increase urine volume
Could treat acute renal failure
Reduce intracranial pressure
Reduce intraocular pressure
Mannitol
Contraindications
CHF
Chronic Renal failure
Pulmonary edema
What transporter is present on the apical membrane of the thick ascending limb?
Na+/K+/Cl- cotransporter
Action of the Na+/K+/Cl- cotransporter helps cause paracellular transport of what substances in the thick ascending limb?
Mg2+ and Ca2+
What is the primary mechanism of action for loop diuretics?
Inhibit the Na+/K+/Cl- cotransporter
Vasodilation – increase renal blood flow (prostaglandin mediated)
Furosemide
MOA
Inhibit the Na+/K+/Cl- cotransporter
Renal vasodilation
Decreases reabsorption of Mg2+ and Ca2+
Furosemide
Pharmacokinetics
Short half life (1-1.5 hrs)
Furosemide
Adverse Effects
Hyponatremia Hypokalemia Hypomagnesemia Metabolic alkalosis Ototoxicity
Furosemide
Clinical Indications
Acute Pulmonary Edema
Edema assoc. with CHF
Acute hypercalcemia
Acute hyperkalemia
List the 4 Loop Diuretics
Furosemide
Bumetanide
Torsemide
Ethacrynic Acid
Why is ethacrynic acid used as a last resort as a loop diuretic?
It is both nephrotoxic and ototoxic
What channel is present on the distal convoluted tubule apical membrane?
Na+/Cl- cotransporter
What channel is present on the distal convoluted tubule basolateral membrane? What receptor is present there?
Na+/K+ ATPase
Na+/Ca2+ antiporter (brings Na+ into cell and Ca2+ into blood)
PTH Receptor is also present on basolateral membrane
Hydrochlorothiazide
MOA
Blocks the Na+/Cl- cotransporter on the apical membrane
Allows for more Ca2+ reabsorption
Hydrochlorothiazide
Adverse Effects
Hyponatremia Hypokalemia Metabolic alkalosis Hyperglycemia Hyperlipidemia Dehydration
Hydrochlorothiazide
Clinical Uses
HTN
CHF
Reduce Ca2+ excretion to prevent kidney stones
List the thiazide diuretics
Hydrochlorothiazide Chlorothiazide Metolazone Indapamide Chlorthalidone
What channels are present on the apical membrane of principal cells of the collecting ducts?
Na+ channels (moving Na+ into the cell)
K+ channels (moving K+ out of the cell and into lumen)
H2O channels, bring H2O into cell
Aldosterone binds its receptor where? What does that cause?
Binds receptors in principal cells of the collecting ducts.
Causes increased transcription of the Na+/K+ ATPase and apical Na+ channels
Intercalated Cells contain what apical transporter? What is it regulated by?
H+ ATPase
Pumps H+ into the luminal fluid
Regulated by aldosterone
How do Carbonic anhydrase inhibitors cause hypokalemia?
They cause an increased conc of Na+ and HCO3- to reach the collecting ducts, which leads to a greater negative luminal potential. This forces more K+ out of the cells into the lumen, thus wasting more K+ and causing hypokalemia
How do thiazide and loop diuretics cause hypokalemia?
Cause an increased delivery of Na+ and Cl- to the collecting ducts, increasing the negative luminal potential in the collecting ducts and pulling more K+ out into the lumen. Causes hypokalemia (K+ wasting)
How do thiazide and loop diuretics cause metabolic alkalosis?
Cause more Na+ and Cl- to reach the collecting ducts, thus increasing the negative luminal potential. Leads to more H+ being pumped out of intercalated cells by the H+ ATPase, thus causing metabolic alkalosis
Where in the nephron do K+ sparing diuretics work?
Collectig tubules
When should K+ sparing diuretics NEVER be given?
DO NOT use K+ sparing diuretics when hyperkalemia is a risk
DO NOT coadminister with an ACE inhibitor
Spironolactone
MOA
Aldosterone receptor antagonist
Anti-androgenic effects
Spironolactone
Adverse Effects
Hyperkalemia Metabolic acidosis Gynecomastic, amenorrhea, impotence GI Upset CNS effects
Spironolactone
Clinical Indications
Primary or Secondary Hyperaldosteronism
Liver cirrhosis – DOC
HTN
Eplerenone
MOA
Aldosterone receptor antagonist
Does NOT have the same anti-androgenic effects that spironolactone does, so there are fewer side effects
How can spironolactone cause metabolic acidosis?
Blocking aldosterone decreases the negative luminal potential.
Leads to less H+ efflux from the intercalated cells, so the H+ accumulates in the blood
Amiloride
MOA
Blocks Na+ channels on principal cells
K+ sparing diuretic because it decreases driving force for K+ to leave cells
Amiloride
Adverse Effects
Hyperkalemia
GI upsets
Muscle cramps
CNS effects
Amiloride
Clinical Indications
Edema
HTN
Usually combined with a loop or thiazide diuretic to prevent K+ loss
Triamterene
MOA
Blocks Na+ channels in principal cells
K+ sparing diuretic because it decreases driving force for K+ to leave cells
ADH Antagonists What class of drugs is now used? List them and specify the receptor they antagonize
Vaptams
V2 receptor antagonists
Tolvaptam
Mozavaptam
Lixivaptam
V1a and V2 receptor antagonist
Conivaptam
ADH Antagonists
Indications
SIADH
Euvolemic or hypervolemic hyponatremia
CHF
ADH Antagonists
Adverse Effects
Hypernatremia Thirst Dry mouth Hypotension Dizziness
What kind of diuretic would you typically give for chronic right heart failure?
Oral Loop diuretic
What kind of diuretic would you typically give for acute left heart failure?
IV Loop diuretic
You need aggressive and rapid therapy
What is hyponatremia clinically defined as?
Serum Na+ concentration less than 136 mEq/L
What kind of hyponatremia may be treated by administration of saline?
Hypovolemic hyponatremia
What drugs are used to treat hyponatremia?
ADH receptor antagonists (Vaptams)
They increase serum Na+ conc and decrease urine osmolality
What kind of diuretic should be used for uncomplicated HTN?
Thiazide diuretic
For patients with diabetes and chronic kidney disease, what hypertensive medications should be used?
Two or more antihypertensive meds…
likely including a thiazide diuretic
What is nephrogenic diabetes insipidus?
Loss of ADH effectivity in principal cells of the collecting tubules
What diuretics should be used to treat nephrogenic diabetes insipidus? Why?
Thiazide diuretics
They may lead to increased Na+ channel synthesis and aquaporin synthesis in principal cells
Kidney stones are mostly made of what?
Calcium
Which diuretics are useful at preventing kidney stones? Why?
Thiazide diuretics are useful at preventing kidney stones because they increase the reabsorption of Ca2+.
Which diuretics have an increased risk of causing kidney stones? Why?
Loop diuretics because they prevent the reabsorption of Ca2+, thus increasing Ca2+ concentration in the lumen of the nephron
What diuretics should be used in hypercalcemia?
Loop diuretics (increase excretion of Ca2+)
What diuretics should be avoided in hypercalcemia?
Thiazide diuretics (increase reabsorption of Ca2+)
